title: Synthesis of 1,4-anthracene-9,10-dione derivatives and their regulation of nitric oxide, IL-1β and TNF-α in activated RAW264.7 cells.
abstract: Mitoxantrone is an anthracenedione antineoplastic and immunosuppressive agent approved for multiple sclerosis treatment. Novel mono- and disubstituted anthraquinone derivatives, analogues of mitoxantrone, were synthesized through the addition of lipophilic amino alcohols and evaluated for their effect on IL-1β, TNF-α and nitric oxide production by LPS/IFN-γ-stimulated RAW264.7 cells. The disubstituted 1,4-anthracene-9,10-dione 10 showed significant inhibition of nitric oxide, TNF-α and IL-1β production at the concentration of 5 μg/mL, with a much lower cytotoxicity than mitoxantrone. The monosubstituted 3, 4, 11, 12 and 13 also displayed a moderate to good inhibitory capacity on IL-1β production. However, the methylated compounds 11, 12 and 13 failed to inhibit the TNF-α production, and compound 13 was the only one to decrease the production of nitric oxide. None of these derivatives was toxic at the tested concentrations. Compounds 10 and 13 had better inhibitory capacity of the inflammatory mediators analyzed, with reliable viability of the cells.
authors.affiliation: Department of Chemistry, ICE, Federal University of Juiz de Fora, Campus Martelos, Juiz de Fora, MG, 36036-330, Brazil.
authors.forename: Taís Arthur
authors.initials: TA
authors.lastname: Corrêa
authors.forename: Caio C S
authors.initials: CC
authors.lastname: Alves
authors.forename: Sandra B R
authors.initials: SB
authors.lastname: Castro
authors.forename: Erick E
authors.initials: EE
authors.lastname: Oliveira
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Franco
authors.forename: Ana P
authors.initials: AP
authors.lastname: Ferreira
authors.forename: Mauro V
authors.initials: MV
authors.lastname: de Almeida
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002460:Cell Line; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide
keywords: IL-1β; RAW264.7; TNF-α; anthraquinone; cytotoxicity; mitoxantrone; nitric oxide